Therapeutics and Biology
Ralph Baric has a primary appointment in the Department of Epidemiology in the Gillings School of Public Health, a joint appointment with the Department of Microbiology and Immunology in the School of Medicine, and is also a member of the Lineberger Comprehensive Cancer Center (LCCC). Much of his research is focused on coronaviruses and the lab is currently working on many aspects of SARS-CoV-2 including model development, mechanistic biology, and identification of potential antivirals and vaccine formulations. Furthermore, because Baric is a renowned expert on coronaviruses, he has served on panels and appeared on many media outlets and public COVID-19 forums. His group published a preliminary report in bioRxiv that highlights the potential therapeutic value of a new antiviral, NHC/EIDD-2801.
Researchers: Ralph Baric
Mark Heise, Professor in the Departments of Genetics and Microbiology and Immunology and member of LCCC is working to develop mouse models of SARS-CoV-2 or testing of antivirals and vaccines. Heise has previously worked to develop mice receptive to MERS and SARS and works collaboratively with Ralph Baric.
Researchers: Ralph Baric, Mark Heise
Aravinda de Silva is a Professor in the Department of Microbiology and Immunology with expertise in the area of mosquito-borne flavivirus and dengue virus vaccines and diagnostics. He is applying this broad-based knowledge of virology and human immunology to develop assays for specific detection of SARS-CoV-2 IgG and IgM antibodies. Furthermore, de Silva is working with Ralph Baric’s group to characterize vaccine responses.
Researchers: Ralph Baric, Aravinda de Silva
Craig Cameron, Jeffrey Houpt Distinguished Professor and Chair of the Department of Microbiology and Immunology, and Jamie Arnold, research associate professor in the UNC Department of Cell Biology and Physiology, has partnered with Riboscience, LLC to screen their library of nucleotide analogues to identify those with efficacy against the SARS CoV-2 replicase, the RNA-dependent RNA-polymerase needed for multiplication of all RNA viruses.
Researchers: Jamie Arnold, Craig Cameron
Nathanial Moorman is an Associate Professor in the Department of Microbiology and Immunology and LCCC member. Moorman is using his expertise to screen for new antiviral agents against SARS-CoV-2 in partnership with Ralph Baric and Mark Heise. This is also a collaboration with the Eshelman School of Pharmacy.
Tim Willson is a Professor at the Structural Genome Consortium-UNC Laboratory where his team is working with UNC virologists to identify drugs that slow the ability of SARS-CoV-2 to multiply inside cells. The Willson group has identified kinase enzymes that are modified by a closely related coronavirus when it infects cells. Drugs that target these enzymes will be tested for anti-viral activity in human lung cells infected with the SARS-CoV-2 that causes COVID-19.
Keywords: host kinases, antiviral drug development
Researchers: Tim Willson
Bryan Roth is the Michael Hooker Distinguished Professor in the Department of Pharmacology, has an appointment in the Eshelman School of Pharmacy, and is the Project Director of the NIMH Psychoactive Drug Screening Program. Roth and his team are profiling candidate drugs to determine mechanism(s) of action which may contribute to therapeutic activity for COVID-19, and are also beginning screens of approved medications to determine if they might inhibit viral interactions with host receptors. The goal of his efforts is to discover medications that are already approved for human-use as potential therapeutics for COVID-19.
Researchers: Bryan Roth
Alex Tropsha is the Associate Dean of Pharmacoinformatics, at the UNC Eshelman School of Pharmacy, and the K.H. Lee Distinguished Professor, Division of Chemical Biology and Medicinal Chemistry. His team is very active in several computational research projects on possible target and drug discovery against SARS-CoV-2 virus, having generated several putative inhibitors of the main protease of the virus that are awaiting experimental confirmation. The Tropsha teams innovative modeling efforts hold promise in both collapsing the time-to-discovery window, and, using data science to identify existing approved medicines that may support recovery from SARS-CoV-2 infection.
Keywords: protease inhibitors of virus, computational modeling
Researchers: Alex Tropsha
Ron Swanstrom is the Charles P. Postelle, Jr. Distinguished Professor of Biochemistry has a joint appointment in the Department of Microbiology and Immunology, and is the Director of the UNC Center for AIDS Research. In collaboration with Ralph Baric’s team, Swanstrom tested a candidate therapeutic NHC/EIDD-2801: a ribonucleoside with broad-spectrum antiviral activity that works by inducing mutations in the viral genome.
Researchers: Ron Swanstrom, Ralph Baric
Sam Lai is the Director, Pharmacoengineering Program, Division of Pharmacoengineering and Molecular Pharmaceutics Assistant Director, Academic Innovation, Eshelman Institute for Innovation Associate Professor, Division of Pharmacoengineering and Molecular Pharmaceutics Adjunct Assistant Professor, UNC Department of Biomedical Engineering. He brings world-class expertise in developing a variety of muco-trapping
monoclonal antibody (mAb) candidates as inhaled immunotherapy against COVID-19. Lai’s team is actively evaluating the first candidate in a hamster efficacy model after positive in vitro data; this compound can be fast-tracked to human studies within 2–3 months, pending support from DoD. In parallel, we are engineering various novel mAbs against COVID19, and also making non-infectious COVID19 that the community can work with.
Keywords: mucus, antiviral drug development, antibody
Researchers: Sam Lai
K.H. Lee, Distinguished Professor, Division of Chemical Biology and Medicinal Chemistry seeks the 1) Identification of potential natural product-based new drugs for treating COVID-19; 2) Select potential anti-COVID-19 compounds from an in-house library containing over 5,000 unique compounds from natural sources and chemical synthesis based on both virtual screening results and rational medicinal chemistry perspectives; 3) Evaluate lead compounds by enzyme-affinity experiments; 4) Develop a series of novel antiviral agents by modifying the potent lead compounds.
Keywords: natural products, enzyme inhibitors
Researchers: K.H. Lee
Rihe Liu is an Associate Professor, Division of Chemical Biology and Medicinal Chemistry and his group is Investigating how to reduce the ‘cytokine storm’ frequently happening in severe COVID-19 cases. Analyzing several other targets on COVID-19, specifically the ACE2 and TMPRSS2 expression areas.
Keywords: cytokines
Researchers: Rihe Liu
Jian Liu is the John & Deborah McNeill, Jr. Distinguished Professor, Division of Chemical Biology and Medicinal Chemistry who explores COVID-19’s spike protein involved in binding to a host’s cell receptors that establishes infection. Recent scientific reporting suggests that heparin sulfate interacts with COVID-19 spike protein and the Liu group plans to study which specific heparin sulfate structure displays the highest affinity to COVID-19 spike protein. Heparin sulfate also attenuates the inflammation induced by COVID-19 infection. It is now known that many patients infected by COVID-19 suffer from uncontrolled inflammation responses in the lung, which leads to lung failure. Using heparin sulfate, the group will explore inhibiting a series of proinflammatory proteins released after COVID-19 infection to reduce the symptoms in patients.
Keywords: viral entry, spike protein, heparin sulfate
Researchers: Jian Liu
J. Victor Garcia-Martinez, Professor in the Division of Infectious Diseases in the Department of Medicine and Angela Wahl, Assistant Professor in the Division of Infectious Disease in the Department of Medicine are both working on developing novel models of SARS-CoV-2 with Ralph Baric to further COVID-19 research. A recent Nature Biotechnology paper describes how Wahl and Garcia-Martinez previously developed a humanized mouse in collaboration with Baric for the in vivo testing of Middle East respiratory syndrome (MERS) coronavirus and other respiratory pathogens.
Researchers: Ralph Baric, J. Victor Garcia-Martinez, Angela Wahl
Angela Kashuba is the Dean of the UNC Eshelman School of Pharmacy, the John A. and Margaret P. McNeill Sr. Distinguished Professor, and Director, Clinical Pharmacology and Analytical Chemistry Core, UNC Center for AIDS Research. In responding to the global pandemic of COVID19 she uses her expertise in mass spectrometry imaging methods to analyze how a potential therapeutic drug might behave in cells to support human recovery from infection.
Keywords: pk analysis of antivirals, mass spec analysis, cell culture
Researchers: Angela Kashuba
Gauri Rao is an Assistant Professor in the Division of Pharmacotherapy and Experiential Education. Her work explores Cellular Pharmacokinetics/Pharmacodelivery (PK/PD) of novel antivirals for COVID-19 in collaborations with Tony Hickey, Sasha Kabanov and Ric Boucher on COVID-19 research projects.
Keywords: pk/pd modeling of inhalational therapy in animal and human subjects, pk/pd modeling, in vivo study design
Researchers: Richard Boucher, Gauri Rao, Anthony Hickey, Alexander Kabanov
Luther Bartelt, Assistant Professor in the Department of Medicine, is spearheading a convalescent serum trial that obtains serum containing antibodies against COVID-19 from individuals who have recovered from COVID-19 and gives it as a therapeutic to patients suffering from COVID-19. Investigators from the UNC Blood Bank and Division of Infectious Diseases are also involved in this study. With a focus on treatment and research, UNC-Chapel Hill has recently created a blood bank from patients who have recovered from COVID-19, which is being used in compassionate care cases as a treatment option for the sickest COVID-19 patients.
Keywords: therapeutics, diagnostics, blood banking
Researchers: Luther Bartelt
Rachel Graham, Assistant Professor in the Department of Epidemiology, examines emerging infectious diseases, specifically SARS and coronavirus. She uses basic science techniques to examine host receptors and disease transmission to identify potential candidates for epidemic surveillance and preventive measures against these deadly infectious diseases.
Keywords: spatial health research, infectious diseases, epidemiological surveillance, coronaviruses
Researchers: Rachel Graham
Michael Emch, Kenan Distinguished Professor in the Departments of Geography and Epidemiology, is examining the value of a potential sero-surveillance project involving all hospitalized patients in the UNC system. The project would take serum from different age strata and assess whether patients had antibodies to COVID-19; it would then follow the population spatially over time as they are readmitted. The model may provide insights into the number of COVID-19 subclinical infections. Dr. Emch is also currently developing new work in spatial data science and infectious disease to understand COVID-19 in Africa.
Keywords: spatial health research, epidemiology
Researchers: Michael Emch
Kathleen Harris, Haar Distinguished Professor in the Department of Sociology, is leading a team using data sets from the National Longitudinal Survey of Adolescent to Adult Health (ADD Health) to build models of COVID-19 disease susceptibility and progression. One project using gene expression data (i.e., RNA) is assembling expression signatures that appear similar to expression signatures found in animal research or human samples related to corona-type infections (like SARS) and which are known signatures related both to the susceptibility and the severity of the virus. Dr. Harris’ team will look for overlap of these signatures in the ADD Health data to identify the genes expressed in response to corona-like infection. They will then examine whether life course factors (e.g., early childhood diseases, environmental exposures, early childhood adversity, etc.) are related to the expression signatures for susceptibility and severity of corona-type virus infections. The work is exploratory in nature and potential outcomes are uncertain. Dr. Harris’ team also plans to collect COVID-19 symptom data while collecting microbiome data from survey participants to drive analyses of symptom data on a nationally-representative sample of adults in their forties.
Keywords: sociology, population health
Researchers: Kathleen Harris
Melinda Beck, Professor, Raza Shaikh, Associate Professor, Beth Mayer-Davis, Cary C. Boshamer Distinguished Professor of Nutrition and Medicine, and Penny Gordon-Larsen, Professor in the Department of Nutrition, are working to understand why people with obesity and diabetes are at higher risk for COVID-19 complications and why they suffer at greater rates than non-obese and non-diabetic people.